Cortisol, a vital stress hormone, is produced in the adrenal cortex and influences numerous processes in the body, including energy supply, blood pressure regulation and electrolyte balance. As a biologically inactive precursor, it must be converted into the active cortisol by the liver.
The discovery and use of cortisone in the 1930s and its first injection in a patient with severe rheumatoid arthritis in 1948 marked the beginning of a new era in medicine. This therapy led to the patient becoming pain-free, which was a revolutionary development. Dr. Edward Kendall, Dr. Philip Hench and Dr. Tadeusz Reichstein were awarded the Nobel Prize for Medicine in 1950 for their work.
Since then, cortisone has played a fundamental role in the treatment of rheumatoid arthritis and other inflammatory rheumatic systemic diseases as well as many other autoimmune, inflammatory and allergic diseases. It influences fundamental processes such as catabolic metabolism, cell division, inflammation regulation and immune defense.
Before the introduction of cortisone, treatment options for diseases such as rheumatoid arthritis and other inflammatory rheumatic systemic diseases were severely limited and often ineffective. Patients suffered from significant pain, inflammation and limited mobility, and the prognosis was often bleak. The introduction of cortisone fundamentally changed this and for the first time offered an effective treatment option that could significantly alleviate patients' suffering.
The discovery and development of cortisone
The history of cortisone began in the 1940s at the Mayo Clinic, where Dr. Edward Kendall and Dr. Philip Hench worked together. Dr. Kendall had already isolated cortisone, a steroid hormone, from the adrenal cortex, but its clinical significance was not yet recognized. Dr. Hench observed that the symptoms of rheumatoid arthritis in his patients decreased during pregnancy or jaundice phases. These observations led to the hypothesis that certain substances in the body could reduce inflammation. The crucial link between these observations and cortisone came when Dr. Hench and Dr. Kendall began testing the hormone on patients with severe rheumatoid arthritis. The first trial in 1948 showed spectacular results: Patients who had previously been confined to bed were able to move again and had significantly less pain. An often-told anecdote from this time tells of a patient who, after treatment with cortisone, threw aside his crutches and took a walk around the hospital room - a moment that illustrates the transformative power of the drug.
This groundbreaking discovery earned Dr. Kendall, Dr. Hench and the chemist Dr. Tadeusz Reichstein, who was also involved in research into steroid hormones, the Nobel Prize in Physiology or Medicine in 1950.
Application and mechanism of action in rheumatology
Prednisolone, a synthetic derivative of cortisone, is one of the most commonly used glucocorticoids in rheumatology. It is used to treat a variety of inflammatory and autoimmune diseases, including rheumatoid arthritis, systemic lupus erythematosus (SLE) and many others.
Mechanism of action of prednisolone
Prednisolone works by inhibiting the expression of pro-inflammatory cytokines and modulating the immune system. Here are some of the key mechanisms:
- Inhibition of pro-inflammatory cytokines: Prednisolone reduces the production and release of cytokines such as tumor necrosis factor-alpha (TNF-α), interleukin-1 (IL-1), interleukin-6 (IL-6) and interleukin-8 (IL-8). These cytokines play a key role in the inflammatory response and tissue damage in rheumatic diseases.
- Suppression of the activation of T lymphocytes: Prednisolone modulates the activation and proliferation of T lymphocytes, which play a central role in the immune response and autoimmunity.
- Stabilization of cell membranes: Prednisolone stabilizes the lysosome membranes and thus prevents the release of proteolytic enzymes that can contribute to tissue damage.
- Inhibition of phospholipase A2: Inhibiting this enzyme reduces the production of arachidonic acid and downstream inflammatory mediators such as prostaglandins and leukotrienes.
Long-term side effects
Although cortisone and its derivatives such as prednisolone offer immense benefits, they are not without risks. Long-term use of glucocorticoids can lead to significant side effects. The main long-term side effects include:
- Osteoporosis: Long-term use can promote bone loss and increase the risk of fractures.
- Hyperglycemia and diabetes: Glucocorticoids can increase blood glucose levels and increase insulin resistance, which can lead to diabetes.
- High blood pressure: The increased sodium and water retention can contribute to high blood pressure.
- Cushing's syndrome: Chronic use of high doses can cause Cushing's syndrome, which is characterized by weight gain, full moon face and central obesity.
- Immunosuppression: Suppression of the immune system increases the risk of infections.
